Reduced expression of bone morphogenetic protein receptor IA in pancreatic cancer is associated with a poor prognosis

BACKGROUND: The expression of SMAD4, the central component of the transforming growth factor-β (TGF-β) and bone morphogenetic protein (BMP) signalling pathways, is lost in 50% of pancreatic cancers and is associated with a poor survival. Although the TGF-β pathway has been extensively studied and characterised in pancreatic cancer, there is very limited data on BMP signalling, a well-known tumour-suppressor pathway. BMP signalling can be lost not only at the level of SMAD4 but also at the level of BMP receptors (BMPRs), as has been described in colorectal cancer. METHODS: We performed immunohistochemical analysis of the expression levels of BMP signalling components in pancreatic cancer and correlated these with survival. We also manipulated the activity of BMP signalling in vitro. RESULTS: Reduced expression of BMPRIA is associated with a significantly worse survival, primarily in a subset of SMAD4-positive cancers. In vitro inactivation of SMAD4-dependent BMP signalling increases proliferation and invasion of pancreatic cancer cells, whereas inactivation of BMP signalling in SMAD4-negative cells does not change the proliferation and invasion or leads to an opposite effect. CONCLUSION: Our data suggest that BMPRIA expression is a good prognostic marker and that the BMP pathway is a potential target for future therapeutic interventions in pancreatic cancer

Achieving Selective Targeting Using Engineered Nanomaterials

The development of Drug Delivery Systems (DDS) able to selectively deliver a controlled amount of a drug only to diseased cells would represent a dramatic development in nanomedicine. One of the multiple challenges still paving the way towards this goal is the elaboration of strategies that would allow targeting with extreme accuracy specific cells, as cancerous cells, among a large variety of closely related ones. In this work, we review the most recent nanotechnology applications aiming at controlling the selectivity of the interaction of delivery nanosystems with cells, with a focus on multivalent targeting. We briefly review thermodynamic models of multivalent interactions and highlight the challenges that still need to be addressed to transfer theoretical design principles into practical applications. In particular, suitable experimental systems based on multivalent models often require the control of the nanocarrier characteristics at the molecular level. Traditional delivery methods, however, fail to provide such degree of control. DNA nanotechnology is a growing field of nanoscience that has witnessed impressive developments in the past decades and has led to major advances in the fabrication of nanostructures and self-assembled systems. Relying on the possibility of controlling their molecular interactions by sequence design, nucleic acids can serve the drug delivery program by providing desired nanostructures with nearly atomic precision. In combination with the recent achievements in the research on DNA aptamers, short nucleic acid sequences isolated to interact selectively with a specific target, DNA nanotechnology is undoubtedly one of the most promising tools for the development of selective DDS.info:eu-repo/semantics/publishe